Advanced materials and chemo-specific designs at the nano/micrometer-scale have ensured revolutionary progress in next-generation clinically relevant technologies. For example, isolating a rare population of cells, like circulating tumor cells (CTCs) from the blood amongst billions of other blood cells, is one of the most complex scientific challenges in cancer diagnostics. The chemical tunability for achieving this degree of exceptional specificity for extra-cellular biomarker interactions demands the utility of advanced entities and multistep reactions both in solution and in the insoluble state. Thus, this review delineates the chemo-specific substrates, chemical methods, and structure–activity relationships (SARs) of chemical platforms used for isolation and enumeration of CTCs in advancing the relevance of liquid biopsy in cancer diagnostics and disease management. We highlight the synthesis of cell-specific, tumor biomarker-based, chemo-specific substrates utilizing functionalized linkers through chemistry-based conjugation strategies. The capacity of these nano/micro substrates to enhance the cell interaction specificity and efficiency with the targeted tumor cells is detailed. Furthermore, this review accounts for the importance of CTC capture and other downstream processes involving genotypic and phenotypic CTC analysis in real-time for the detection of the early onset of metastases progression and chemotherapy treatment response, and for monitoring progression free-survival (PFS), disease-free survival (DFS), and eventually overall survival (OS) in cancer patients.

中文翻译：

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循环肿瘤细胞计数的化学特异性设计：液体活检的进展

纳米/微米级的先进材料和化学特异性设计确保了下一代临床相关技术的革命性进步。例如，从数十亿其他血细胞中的血液中分离出罕见的细胞群，如循环肿瘤细胞 (CTC)，是癌症诊断中最复杂的科学挑战之一。实现这种对细胞外生物标志物相互作用的特殊特异性的化学可调性需要在溶液和不溶状态下使用先进的实体和多步反应。因此，本综述描述了化学特异性底物、化学方法、用于分离和计数 CTC 的化学平台的构效关系 (SAR)，以提高液体活检在癌症诊断和疾病管理中的相关性。我们强调通过基于化学的偶联策略利用功能化接头合成细胞特异性、基于肿瘤生物标志物的化学特异性底物。详细介绍了这些纳米/微米底物增强细胞与靶向肿瘤细胞相互作用特异性和效率的能力。此外，本综述还说明了 CTC 捕获和其他涉及实时基因型和表型 CTC 分析的下游过程的重要性，用于检测转移进展的早期发作和化疗治疗反应，以及监测无进展生存 (PFS) ,